NOD.129(B6)-Tnfsf4^tm1Shr/DoiJ

Stock number: 005075
Product name: NOD.Ox40L^null
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research

Description

These Tnfsf4 knock-out mice are completely protected from diabetes and histological evaluation seldom shows insulitis.

Detailed description

Tnfsf4^tm1Shrhomozygous mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. There is no detectable expression of Tnfsf4 on activated dendritic cells, T-cells and B-cells derived from spleen or lymph nodes by FAC analysis or ELISA. Additionally, the number of B-cells, T-cells, T-cell subsets and expression of CD25 and CD69 in spleen and lymph nodes are comparable to NOD controls. All Tnfsf4 homozygous mice are completely protected from diabetes and histological evaluation seldom shows insulitis when compared to wild-type controls, which exhibit a normal NOD like diabetes incidence and onset.

This model is useful for studying co-stimulation, dendritic cell function and the role of Tnfsf4 on CD4 positive T cell responses in Type 1 Diabetes.

Development

A construct containing a neomycin expression cassette replaced the entire extracellular domain and part of the 3' untranslated region of Tnfsf4 (commonly referred to as Ox40l and cloned from 129/Sv mouse genomic library) was transfected into J1 embryonic stem cells (ES cells). These ES cells were injected into C57BL/6 blastocysts. To establish a colony with germ line transmission, chimeric mice were backcrossed to 129/Sv (Chen et, al, 1999). Martin-Orozco et al. 2003, subsequently backcrossed this mutation to NOD/Lt. A genome wide scan confirmed that markers for Idd1, Idd3, Idd5 and Idd10 were homozygous for the NOD allele. In 2004, the Type 1 Diabetes Resource received NOD.129(B6)-Tnfsf4^tm1Shr/DoiJ at generation N8F4.

Allele

Symbol: Tnfsf4^tm1Shr
Name: targeted mutation 1, Arlene H Sharpe
MGI accession ID: MGI:2683777
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Tnfsf4
Marker name: tumor necrosis factor (ligand) superfamily, member 4
Chromosome: 1
Strain of origin: 129S4/SvJae
Molecular note: A neomycin selection cassette inserted by homologous recombination replaced the exon encoding the entire extracellular domain and a portion of the 3' untranslated region. Protein was undetected by flow cytometric analysis of activated homozygous mutant dendritic cells.